Rocuronium bromide is a novel mono-quaternary ammonium muscle relaxant and is used as an anesthetic adjuvant drug for tracheal intubation during anesthetization and muscle relaxation in surgical operation. Rocuronium bromide is a non-depolarizing muscle relaxant used clinically with the most rapid onset. The characteristics thereof include rapid onset, rapid recovery, weak inhibitory effects on cardiovascular system, and no histamine releasing effects. This drug is the most widely used muscle relaxant internationally, and is the first-ranked muscle relaxant in consumption used in North America and most European countries. The chemical formula thereof is as follows:

European patent EP 0287150 initially discloses the preparation method and use thereof, in which 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α-ol-17β-acetate is reacted with 3-bromopropene in dichloromethane for 22 h, wherein the molar volume ratio of the three materials is 1 mol:8.2 mol:10 L. Separation by column chromatography obtained the target product. This method has certain disadvantages: high equivalent amount of 3-bromopropene is applied; the reaction time is long; the treatment needs column separation, which is not conducive to practical productions. U.S. Pat. No. 7,579,461 involves reacting 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α-ol-17β-acetate with bromopropene in acetone under reflux to react for 10 h, wherein the molar volume ratio of the three materials is 1 mol:2.3 mol:5 L, removing the solvent under reduced pressure to give rocuronium bromide. Although less equivalent amount of 3-bromopropene is applied in this method, the reaction process requires heating under reflux and longer reaction time. Rocuronium bromide is poor in thermal stability, which results in large amount of impurities in the reaction. The method described in U.S. Pat. No. 7,642,246 is that 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α-ol-17β-acetate is reacted with bromopropene and solid powder of sodium carbonate in dichloromethane under the protection of nitrogen gas for 24 h, wherein molar volume ratio of the four materials is 1 mol:2 mol:4.6 mol:2.3 L. In this method, since it is the two-phase reaction, and has a long reaction time and a low conversion ratio. Chinese patent CN 101323636 discloses that 2β-(4-morpholinyl)-16β-(1-pyrrolidinyl)-5α-androstan-3α-ol-17β-acetate is reacted with bromopropene in ethyl ether at ambient temperature for 2 days, wherein the molar volume ratio of the three materials is 1 mol:5.6 mol:9.8 L, and when the reaction is completed, half of the solvent is removed under reduced pressure, and the residue is recrystallized from acetone to give the target product. Also, reaction time of this method is too long to be conducive to industrialized production.
It can be seen from the methods reported by currently published literatures for technical information that in quaterisation reactions, large amount of solvent and 3-bromopropene are generally required to be added to perform such reactions, and the reaction time is quite long and the aftertreatment is cumbersome, and thus they are not conducive to industrialized production. In addition, 3-bromopropene is a potentially genotoxic substance, which will lead to excessive residue in final products if it is employed in large amount in the reaction. The present invention provides a method for reducing the application amount of 3-bromopropene and the reaction time, while ensuring the yield and purity of rocuronium bromide, so as to further improve the production efficiency, reduce the production cost, and simplify the operation. According to the method of the present patent, the residue of 3-bromopropene in rocuronium bromide can be controlled below 10 ppm.